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A highly stereocontrolled synthesis of α-hydroxycyclopropanes possessing a trifluoromethyl group
Tetrahedron: Asymmchr Vol. 1. No.6, pp351-354.1990 Printed in Great Britain
0!957-4166,?M $3.00t.00 Pergamon Press pk
A HIGHLY STEREOCONTROLLED SYNTHESIS OF a-HYDROXYCYCLOPROPANES POSSESSING A TRIFLUOROMETHYL GROUP Takashi Yamazaki, Jenq Tain Lin, Mitsunori Takeda’, and Tomoya Kitazume* Department of Bioengineering, Tokyo Institute of Technology Ookayama, Meguro-ku, Tokyo 152, Japan (Received 20 April 1990)
Abstract. The preparation of optically pure syn and anti-a-hydroxycyclopropanes possessing a trifluoromethyl group from stereoisomers of optically pure allylic alcohols by samarium-based carbenoids is described.
The stereoselective construction of organofluorine compounds is currently of fundamental importance in such fields as the preparation of bioactive materials and ferroelectric liquid crystalsls5. In particular, considerable attention is being focussed on the search for synthetic methods for the assembly of contiguous stereocentres with high relative as well as absolute stereocontrol. However, only a few methods are known for the control of stereochemistry of fluorine containing molecules giving the diastereomeric and/or enantiomer anti(erythro) or syn(threo) configuration6-9. We report herein the stereocontrolled synthesis of syn and/or anti cyclopropyl carbinols possessing a trifluoromethyl group. We desired a stereochemically controlled synthesis from starting materials of known absolute configuration which would eliminate the need for diastereomeric separation. Therefore, we chose to utilize the hydroxy-directed cyclopropanation*” of (R)or (S)-(E)- and/or (R)- or (S)-(Z)-allylic alcohols” possessing a trifluoromethyl group. These substrates were found to have a dramatic effect on diastereoselectivity of the cyclopropanation, giving only syn-isomer via the Houk model shown in Figure I. In our case, we believe that samarium metal is more tightly coordinated with the oxygen atom in the above Houk model, giving rise to the higher diastereoselectivity. 351
352
T. YMAZM et al.
No previous studies have examined the stereocontrolled synthesis of the anti isomers (4). The syn isomers were oxidized with oxalyl chloride-dimethyl sulphoxide, giving the ketones(3) (Scheme). To achieve the desired stereocontrolled conversion to (4), we investigated the transformation of the optically pure cyclopropyl ketones (3), using a variety of reducing reagents. As the consequence, we found that L-selectride gave by far the highest stereoselection. The desired stereocontrolled products were obtained in moderate to good yields (Table).
OH
OH
a)= b) R’
1
2
R’
a)Sm,CH&,THF,O”C,Ih b)r.t.,lh
OH
0
c) M
R
CF
I
2
3
p 5 d) Rw R - CF 3 R’ 4 c), , hG#O, Et$J , -5o- 0°C d) Gselectide , EtOH
Scheme
R’
353
a-Hydroxycyclopropanes
Table
Compd. R
R
No (abs)a
2 CR) (S)
Synthesis of cyclopropyl carbinols
NMR chemical shift
Yield [alD2’ (%I
MeOH
“F
Sppmb
‘H Gppm (J :
Hz)
H H
Ph Ph
87 60
+57.9 ( 1 . 0 4 ) -46.4 (1.12)
0.82(d)
(R) 0)
Ph Ph
H H
86 87
+124.7(1.01) -118.9(1.01)
1.08(d) 0.94-1.29(2H,m),l.46(1H,ddt J=6.5,J=8.9,J=8.9),2.12(1H,d), 2.37,3.19(2H),7.29(ArH)
CR) (S)
H H
‘gH13 C6H13
92 92
+12.2 ( 1 . 1 3 ) -16.7 (1.12)
1.05(d)
(R) (S)
‘gH13 H ‘gH13 H
83 89
+2.90 ( 1 . 1 4 ) -2.20 (1.16)
1.07(d)
H H
Ph Ph
46 38
+13.4 (1.03) - 9 . 7 3 (1,07)
1.03(d) ll.ll-1.44(3H,m),2.02-2.12 (lH,d,J=5.8),3.58(1H,dq,J= 12.8),7.08-7.32(ArH)
(S)
Ph
H
45
i-23.7 (0.92)
0.75(d) 0.94-l .63(2H,m),l.96(jH,d,J = 4.8),2.39(1H,dt,J=7.5,5=8.3 2.12,3.13(2H),7.37(ArH)
(S)
H
‘gH13
34
+5.70 ( 0 . 9 3 )
1.13(d) 0.75-1.68(17H,m),2.49(lH,
4 (S) (R)
0.93-l .50(3H,m),2.08( lH,dt, J=6.6,J=5.2), 2.24(1H,d),3.67 (lH,dq,J=12.6),7.25(ArH)
0.72-1.57(17H,m),2.48 bs),3.32(lH,J=11.9)
(lH,
0.70-1.89(17H,m),2.28(1H, bs),3.52(1H,dq,J=13.1)
bs),3.36(1H,dq,J=l1.7)
(S)
C6H13 H
37
+5.31 ( 1 . 1 5 )
1.07(d) 0.72-l .85( 17H,m)2.43( 1 H, bs),3.43(1H,dq,J=13.9)
a) absolute configuration at C-l b) 6 ppm from ext. CF3C02H in CDCIQ
T. YMAZAKI et al.
354
(CF3)R3
OH
OH R2 Rl
SYn
R2
Anti
Rl
Fig. 1 RlzFERENm 1. “Biomedicinal Aspects of Fluorine Chemistry,” R. Filler, ; Y. Kobayashi, Eds. : Kodansha and Elsevier Biomedical: Amsterdam, 1982. J. T. Welch, Tetrahedron, 43, 3123 (1987). C. Walsh, Tetrahedron, 38, 871 (1982). K. Yoshino, M. Ozaki, H. Taniguchi, M. Ito, K. Satoh, N. Yamasaki, T. Kitazume, Jpn. J. Appl. Phys., 26, L77 (1987). 5. K. Yoshino, M. Ozaki, H. Taniguchi, M. Ito, K. Satoh, N. Yamasaki, T. Kitazume, Chemistry express, 2, 53 (1987). 6. (a) J. T. Welch, K. W. Seper, Tetrahedron Lett., 25, 5247 (1984). (b) J. T. Welch, K. W. Seper, S. Eswarakrishnan, J. Samartino, J. Org. Chem., 49, 4720 (1984). (c) J. T. Welch, S. Eswarakrishnan, J. Chem. Sot. Chem. Sot., 15, 3964 (1953) 7. J. Hine, W. H. Brader, Jr. J. Am. Chem. Sot., 15, 3964 (1953). 8. F. G. Bordwell, W. H. Brannen, Jr. J. Am. Chem. Sot., 86, 4645 (1964). 9. (a) T. Kitazume, T. Sato, T. Kobayashi, J. T. Lin, J. Org. Chem., i_L, 1003 (1986). (b) J. T. Lin, T. Yamazaki, T. Kitazume, J. Org. Chem., 52, 3211 (1987). (c) T. Kitazume, T. Kobayashi, T. Yamamoto, T. Yamazaki, J. Org. Chem., 52, 3218 (1987). (d) T. Kitazume, T. Ikeya, K. Murata, J. Chem. Sot. Chem. Commun., 1331 (1986). (e) T. Kitazume, T. Ikeya, J. Org. Chem., 53, 2350 (1988). (f) T. Yamazaki, T. Yamamoto, T. Kitazume, J. Org. Chem., 2, 83 (1989). IO. G. A. Molander, J. B. Etter, J. Org. Chem., 2, 3944 (1987). 1 1 T. Kitazume, M. Takeda, J. T. Lin, T. Yamazaki, J. Fluorine Chem., .Q, 177 (1989). 2. 3. 4.
0!957-4166,?M $3.00t.00 Pergamon Press pk
A HIGHLY STEREOCONTROLLED SYNTHESIS OF a-HYDROXYCYCLOPROPANES POSSESSING A TRIFLUOROMETHYL GROUP Takashi Yamazaki, Jenq Tain Lin, Mitsunori Takeda’, and Tomoya Kitazume* Department of Bioengineering, Tokyo Institute of Technology Ookayama, Meguro-ku, Tokyo 152, Japan (Received 20 April 1990)
Abstract. The preparation of optically pure syn and anti-a-hydroxycyclopropanes possessing a trifluoromethyl group from stereoisomers of optically pure allylic alcohols by samarium-based carbenoids is described.
The stereoselective construction of organofluorine compounds is currently of fundamental importance in such fields as the preparation of bioactive materials and ferroelectric liquid crystalsls5. In particular, considerable attention is being focussed on the search for synthetic methods for the assembly of contiguous stereocentres with high relative as well as absolute stereocontrol. However, only a few methods are known for the control of stereochemistry of fluorine containing molecules giving the diastereomeric and/or enantiomer anti(erythro) or syn(threo) configuration6-9. We report herein the stereocontrolled synthesis of syn and/or anti cyclopropyl carbinols possessing a trifluoromethyl group. We desired a stereochemically controlled synthesis from starting materials of known absolute configuration which would eliminate the need for diastereomeric separation. Therefore, we chose to utilize the hydroxy-directed cyclopropanation*” of (R)or (S)-(E)- and/or (R)- or (S)-(Z)-allylic alcohols” possessing a trifluoromethyl group. These substrates were found to have a dramatic effect on diastereoselectivity of the cyclopropanation, giving only syn-isomer via the Houk model shown in Figure I. In our case, we believe that samarium metal is more tightly coordinated with the oxygen atom in the above Houk model, giving rise to the higher diastereoselectivity. 351
352
T. YMAZM et al.
No previous studies have examined the stereocontrolled synthesis of the anti isomers (4). The syn isomers were oxidized with oxalyl chloride-dimethyl sulphoxide, giving the ketones(3) (Scheme). To achieve the desired stereocontrolled conversion to (4), we investigated the transformation of the optically pure cyclopropyl ketones (3), using a variety of reducing reagents. As the consequence, we found that L-selectride gave by far the highest stereoselection. The desired stereocontrolled products were obtained in moderate to good yields (Table).
OH
OH
a)= b) R’
1
2
R’
a)Sm,CH&,THF,O”C,Ih b)r.t.,lh
OH
0
c) M
R
CF
I
2
3
p 5 d) Rw R - CF 3 R’ 4 c)
Scheme
R’
353
a-Hydroxycyclopropanes
Table
Compd. R
R
No (abs)a
2 CR) (S)
Synthesis of cyclopropyl carbinols
NMR chemical shift
Yield [alD2’ (%I
MeOH
“F
Sppmb
‘H Gppm (J :
Hz)
H H
Ph Ph
87 60
+57.9 ( 1 . 0 4 ) -46.4 (1.12)
0.82(d)
(R) 0)
Ph Ph
H H
86 87
+124.7(1.01) -118.9(1.01)
1.08(d) 0.94-1.29(2H,m),l.46(1H,ddt J=6.5,J=8.9,J=8.9),2.12(1H,d), 2.37,3.19(2H),7.29(ArH)
CR) (S)
H H
‘gH13 C6H13
92 92
+12.2 ( 1 . 1 3 ) -16.7 (1.12)
1.05(d)
(R) (S)
‘gH13 H ‘gH13 H
83 89
+2.90 ( 1 . 1 4 ) -2.20 (1.16)
1.07(d)
H H
Ph Ph
46 38
+13.4 (1.03) - 9 . 7 3 (1,07)
1.03(d) ll.ll-1.44(3H,m),2.02-2.12 (lH,d,J=5.8),3.58(1H,dq,J= 12.8),7.08-7.32(ArH)
(S)
Ph
H
45
i-23.7 (0.92)
0.75(d) 0.94-l .63(2H,m),l.96(jH,d,J = 4.8),2.39(1H,dt,J=7.5,5=8.3 2.12,3.13(2H),7.37(ArH)
(S)
H
‘gH13
34
+5.70 ( 0 . 9 3 )
1.13(d) 0.75-1.68(17H,m),2.49(lH,
4 (S) (R)
0.93-l .50(3H,m),2.08( lH,dt, J=6.6,J=5.2), 2.24(1H,d),3.67 (lH,dq,J=12.6),7.25(ArH)
0.72-1.57(17H,m),2.48 bs),3.32(lH,J=11.9)
(lH,
0.70-1.89(17H,m),2.28(1H, bs),3.52(1H,dq,J=13.1)
bs),3.36(1H,dq,J=l1.7)
(S)
C6H13 H
37
+5.31 ( 1 . 1 5 )
1.07(d) 0.72-l .85( 17H,m)2.43( 1 H, bs),3.43(1H,dq,J=13.9)
a) absolute configuration at C-l b) 6 ppm from ext. CF3C02H in CDCIQ
T. YMAZAKI et al.
354
(CF3)R3
OH
OH R2 Rl
SYn
R2
Anti
Rl
Fig. 1 RlzFERENm 1. “Biomedicinal Aspects of Fluorine Chemistry,” R. Filler, ; Y. Kobayashi, Eds. : Kodansha and Elsevier Biomedical: Amsterdam, 1982. J. T. Welch, Tetrahedron, 43, 3123 (1987). C. Walsh, Tetrahedron, 38, 871 (1982). K. Yoshino, M. Ozaki, H. Taniguchi, M. Ito, K. Satoh, N. Yamasaki, T. Kitazume, Jpn. J. Appl. Phys., 26, L77 (1987). 5. K. Yoshino, M. Ozaki, H. Taniguchi, M. Ito, K. Satoh, N. Yamasaki, T. Kitazume, Chemistry express, 2, 53 (1987). 6. (a) J. T. Welch, K. W. Seper, Tetrahedron Lett., 25, 5247 (1984). (b) J. T. Welch, K. W. Seper, S. Eswarakrishnan, J. Samartino, J. Org. Chem., 49, 4720 (1984). (c) J. T. Welch, S. Eswarakrishnan, J. Chem. Sot. Chem. Sot., 15, 3964 (1953) 7. J. Hine, W. H. Brader, Jr. J. Am. Chem. Sot., 15, 3964 (1953). 8. F. G. Bordwell, W. H. Brannen, Jr. J. Am. Chem. Sot., 86, 4645 (1964). 9. (a) T. Kitazume, T. Sato, T. Kobayashi, J. T. Lin, J. Org. Chem., i_L, 1003 (1986). (b) J. T. Lin, T. Yamazaki, T. Kitazume, J. Org. Chem., 52, 3211 (1987). (c) T. Kitazume, T. Kobayashi, T. Yamamoto, T. Yamazaki, J. Org. Chem., 52, 3218 (1987). (d) T. Kitazume, T. Ikeya, K. Murata, J. Chem. Sot. Chem. Commun., 1331 (1986). (e) T. Kitazume, T. Ikeya, J. Org. Chem., 53, 2350 (1988). (f) T. Yamazaki, T. Yamamoto, T. Kitazume, J. Org. Chem., 2, 83 (1989). IO. G. A. Molander, J. B. Etter, J. Org. Chem., 2, 3944 (1987). 1 1 T. Kitazume, M. Takeda, J. T. Lin, T. Yamazaki, J. Fluorine Chem., .Q, 177 (1989). 2. 3. 4.